Tuesday, January 13, 2015

Friendly gut microbe defends against Vibrio cholerae infection

This is a very interesting study from journal Nature. It comes from the famous Jeffrey Gordon's lab at the Washington University School of Medicine, St. Louis.

Usually when we think about the infectious microbes and how to deal with them, we are usually considering antibiotics or vaccination. However, in nature everything is interconnected and mutually dependent, even if any such evolutionary relationships are not immediately obvious.

In nature, if one considers microbial communities, different species can sense each others presence and can influence each others biology. The most widely described such phenomenon is called quorum sensing wherein microbial community can sense its members density and influence and self-adjust its own or others replication kinetics. There are intra-species and inter-species mechanisms of quorum sensing.

The authors has collected and analysed gut microbiota community from stool (fecal) samples from healthy or Vibrio cholerae-infected patients (collection time ranged from diarrhoeal phase to recovery phase). This analysis showed that abundance of 14 gut microbial species correlated with the recovery from Vibrio cholerae dierrhoeal phase.

Using germ-free mice recolonization strategy the authors found that one of the gut microbial species in particular, Ruminococcus Obeum (R. Obeum), restricted Vibrio cholerae colonization in gnotobiotic mice.

The authors found that in presence of Vibrio cholerae infection, R. Obeum up-regulated LuxS gene responsible for the inter-species mechanism of quorum sensing through autoinducer-2 (AI-2) synthesis.

To directly test R. obeum LuxS involvement in restricting expression of virulence factors in V. cholerae, the authors cloned R. obeums LuxS (or V. cholerae LuxS, as a control) into mutant E. coli deficient its own AI-2. Both in vitro and in vivo experiments showed that in presence of R. obeum-derived LuxS gene in mutant E.coli, V. cholerae's replication and expression of virulence factors were reduced during co-culture or co-colonization.

Finally, the authors found that restriction of V. cholerae infection was mediated through a new mechanism involving quorum sensing transcriptional regulator VqmA in V. cholerae.

In summary, the results highlight the new mode of treating infectious agents with the help our own gut microbial friends.